Author

Date on Master's Thesis/Doctoral Dissertation

Document Type

Degree Name

Department

Committee Chair

Giridharan, Guruprasad Anapathur

Author's Keywords

Ex vivo lung perfusion; Organ preservation; Lung transplantation

Subject

Lungs--Transplantation; Lungs--Physiology; Lungs--Preservation

Abstract

Introduction Ex vivo lung perfusion (EVLP) has the potential to increase the donor pool for lung transplantation by facilitating extended evaluation of marginal organs. Current methodology employs continuous flow pumps for perfusion. In vivo, continuous flow has been shown to increase pulmonary vascular resistance (PVR). Thus, pulsatile flow EVLP may reduce PVR and improve organ preservation by providing physiologic flow morphology. Methods Lung blocks harvested from male, Yorkshire pigs were allocated into continuous (CF, n=3) and pulsatile flow (PF, n=4) groups. Lungs were ventilated at 4-5 mL/kg, 30% FiO2 and perfused with an acellular, albumin-based solution corrected for osmolarity, acid/base balance, and CO2 concentration (=19 hours at 30°C). Prostaglandin E2 and 30% albumin were infused continuously at 250 ?g/hr and 100 mL/hr, respectively. Hemodynamic, respiratory, and blood gas parameters were recorded hourly. Parenchymal biopsies were used for quantification of wet: dry ratio and IL-6, IL-8, and TNF-a using ELISA. Results ?PO2/FoO2 in mmHg was 261±47 and 313±37 at baseline and 174±36 and 152±36 at hour 12 for CF and PF, respectively. Wet: dry ratio was 5.53±0.56 and 6.06±0.09 at baseline and 5.27±0.48 and 5.12±0.40 at hour 12 for CF and PF, respectively. Average PVR in Woods Units was 15.17±1.33 and 13.60±1.91 over the 12 hour test period for CF and PF groups, respectively. Peak airway pressure (PAWP) in cm H2O was 17±1.15 and 16±0.75 at baseline and 21±1.67 and 21±0.41 at hour 12 for CF and PF, respectively. There were no discernable differences in TNF-a, IL-6, and IL-8 concentrations, PVR, ?PO2/FiO2, wet: dry ratio, and PAWP between CF and PF. Conclusion EVLP system successfully maintained lungs up to 19 hours using a modified perfusate. These data suggest PF does not offer benefits over CF for prolonged ex vivo lung preservation.